Celiac Disease (CD) is an autoimmune disorder that affects approximately 1% of the worldwide population. The α-gliadins of wheat contain the 33-mer peptide, the most active peptide in CD both in ...adults and pediatric patients. In this study, we have characterized the variants and expression profile of an α-gliadins amplicon, harboring the 33-mer peptide, in two low-gliadin RNAi wheat lines, under two different Nitrogen (N) treatments. We estimated that the amplicon expands 45 different α-gliadin variants with high variability due to length, randomly distributed SNPs, and the presence of encoded CD epitopes. Expression of this amplicon is reduced in both RNAi lines in comparison to the wild type. High N treatment significantly increases transcripts of the amplicon in the wild type, but not in the transgenic lines. Classification of α-gliadin variants, considering the number of epitopes, revealed that amplicon variants containing the full complement of 33-mer peptide were affected by N treatment, increasing their expression when N was increased. Line D793 provided higher and more stable silencing through different N fertilization regimes, expressing fewer CD epitopes than D783. Results of this study are important for better understanding of RNAi α-gliadin silencing in response to N treatments, and for undertaking new strategies by RNAi or CRISPR/Cas toward obtaining new varieties suitable for people suffering gluten intolerances.
Purpose
To evaluate the impact of trabecular micro bypass stents (iStent Inject) on refractive outcomes with toric intraocular lens (IOL) in glaucomatous eyes.
Methods
We identified glaucomatous eyes ...receiving a toric IOL between October 2017 and December 2020. Eyes with iStent implantation were included in the study group and eyes undergoing isolated phacoemulsification served as controls. Corrected and uncorrected visual acuity, manifest refraction, intraocular pressure (IOP), and number of hypotensive drugs three months after surgery were evaluated.
Results
26 eyes comprised the study group and 41 eyes the control group. Mean postoperative refractive cylinder was 0.26D in the control and 0.11D in the iStent group, with 63% and 85% of eyes with a cylinder of 0 and 85% and 92% of eyes with a cylinder ≤ 0.5D respectively. The mean absolute difference between target and outcome spherical equivalent was 0.26D in the control and 0.22D in the iStent group, with all eyes within 0.75D of target. LogMar uncorrected postoperative vision in eyes targeted for emmetropia was 0.04 in the control and 0.03 in the iStent group. There was a statistically significant reduction in IOP and number of hypotensive drugs in both groups, with a mean decrease in IOP of 8.6% in the control and 15.7% in the iStent group. The number of hypotensive drugs dropped from 1.63 ± 0.80 to 1.34 ± 0.91 in the control group and from 2.12 ± 0.65 to 0.44 ± 0.71 in the iStent group.
Conclusion
Toric IOLs provide predictable refractive outcomes in glaucomatous eyes undergoing combined phacoemulsification with iStent implantation, reducing postoperative spectacle dependence.
Commercial and residential building is one of the four major final energy consumption and end-use sectors. In this sector, cooling loads represent an important part of the energy consumption, and ...therefore, they must be minimized, improving the energy efficiency of buildings. Ventilated façades are one of the most widely used passive elements that are integrated into buildings, precisely with the aim of reducing these loads. This reduction is due to the airflow induced in the air cavity by the buoyancy forces, when the solar radiation heats the outer layer of the façade. In the open joint ventilated facades (OJVF), ventilation is attained through the open joints between the panels composing the outer layer. Despite the steadily growing research in the characterization of this type of system, few studies combine the numerical modelling of OJVF with experimental results for the assessment of the airflow in the ventilated cavities. This paper experimentally validates a numerical simulation model of an OJVF. Firstly, the façade performance has been experimentally assessed in a laboratory model determining the temperatures in the panels and air gap and measuring the flow field at the gap using particle image velocimetry (PIV) techniques. Secondly, a numerical model has been developed using advanced Computational Fluid Dynamics (CFD) simulation tools. Finally, an experimental validation of the numerical model has been done. Experimental and numerical results are compared in different planes inside the ventilated cavity. The discrete ordinates (DO) radiation model and the k-ε renormalisation group (RNG) turbulence model better adjust the simulated results to the experimental ones.
Genetic diagnosis of inherited platelet disorders (IPDs) is mainly performed by high-throughput sequencing (HTS). These short-read–based sequencing methods sometimes fail to characterize the genetics ...of the disease.
To evaluate nanopore long-read DNA sequencing for characterization of structural variants (SVs) in patients with IPDs.
Four patients with a clinical and laboratory diagnosis of Glanzmann thrombasthenia (GT) (P1 and P2) and Hermansky–Pudlak syndrome (HPS) (P3 and P4) in whom HTS missed the underlying molecular cause were included. DNA was analyzed by both standard HTS and nanopore sequencing on a MinION device (Oxford Nanopore Technologies) after enrichment of DNA spanning regions covering GT and HPS genes.
In patients with GT, HTS identified only 1 heterozygous ITGB3 splice variant c.2301+1G>C in P2. In patients with HPS, a homozygous deletion in HPS5 was suspected in P3, and 2 heterozygous HPS3 variants, c.2464C>T (p.Arg822∗) and a deletion affecting 2 exons, were reported in P4. Nanopore sequencing revealed a complex SV affecting exons 2 to 6 in ITGB3 (deletion-inversion-duplication) in homozygosity in P1 and compound heterozygosity with the splice variant in P2. In the 2 patients with HPS, nanopore defined the length of the SVs, which were characterized at nucleotide resolution. This allowed the identification of repetitive Alu elements at the breakpoints and the design of specific polymerase chain reactions for family screening.
The nanopore technology overcomes the limitations of standard short-read sequencing techniques in SV characterization. Using nanopore, we characterized novel defects in ITGB3, HPS5, and HPS3, highlighting the utility of long-read sequencing as an additional diagnostic tool in IPDs.
To watch a person doing an activity has an impact on the viewer. In fact, the film industry hinges on viewers looking at characters doing all sorts of narrative activities. From previous works, we ...know that media and non-media professionals perceive differently audiovisuals with cuts. Media professionals present a lower eye-blink rate, a lower activity in frontal and central cortical areas, and a more organized functional brain connectivity when watching audiovisual cuts. Here, we aimed to determine how audiovisuals with no formal interruptions such as cuts were perceived by media and non-media professionals. Moreover, we wondered how motor actions of characters in films would have an impact on the brain activities of the two groups of observers. We presented a narrative with 24 motor actions in a one-shot movie in wide shot with no cuts to 40 participants. We recorded the electroencephalographic (EEG) activity of the participants and analyzed it for the periods corresponding to the 24 motor actions (24 actions × 40 participants = 960 potential trials). In accordance with collected results, we observed differences in the EEG activity of the left primary motor cortex. A spectral analysis of recorded EEG traces indicated the presence of significant differences in the beta band between the two groups after the onset of the motor activities, while no such differences were found in the alpha band. We concluded that media expertise is related with the beta band identified in the EEG activity of the left primary motor cortex and the observation of motor actions in videos.
PurposeThe numerical format in which risks are communicated can affect risk comprehension and perceptions of medical professionals. We investigated what numerical formats are used to report absolute ...risks in empirical articles, estimated the frequency of biasing formats and rated the quality of figures used to display the risks.DesignDescriptive study of reporting practices.MethodWe randomly sampled articles published in seven leading orthopaedic surgery journals during a period of 13 years. From these, we selected articles that reported group comparisons on a binary outcome (eg, revision rates in two groups) and recorded the numerical format used to communicate the absolute risks in the results section. The quality of figures was assessed according to published guidelines for transparent visual aids design.Outcome measuresPrevalence of information formats and quality of figures.ResultsThe final sample consisted of 507 articles, of which 14% reported level 1 evidence, 13% level 2 and 73% level 3 or lower. The majority of articles compared groups of different sizes (90%), reported both raw numbers and percentages (64%) and did not report the group sizes alongside (50%). Fifteen per cent of articles used two formats identified as biasing: only raw numbers (8%, ‘90 patients vs 100 patients’) or raw numbers reported alongside different group sizes (7%, ‘90 out of 340 patients vs 100 out of 490 patients’). The prevalence of these formats decreased in more recent publications. Figures (n=79) had on average two faults that could distort comprehension, and the majority were rated as biasing.ConclusionAuthors use a variety of formats to report absolute risks in scientific articles and are likely not aware of how some formats and graph design features can distort comprehension. Biases can be reduced if journals adopt guidelines for transparent risk communication but more research is needed into the effects of different formats.
Traumatic brain injury represents one of the main health problems in developed countries. Growth hormone (GH) and rehabilitation have been claimed to significantly contribute to the recovery of lost ...motor function after acquired brain injury, but the mechanisms by which this occurs are not well understood. In this work, we have investigated cell proliferation in the piriform cortex (PC) of adult rats with ablation of the frontal motor cortex treated with GH and rehabilitation, in order to evaluate if this region of the brain, related to the sense of smell, could be involved in benefits of GH treatment. Male rats were either ablated the frontal motor cortex in the dominant hemisphere or sham-operated and treated with GH or vehicle at 35 days post-injury (dpi) for five days. At 36 dpi, all rats received daily injections of bromodeoxyuridine (BrdU) for four days. We assessed motor function through the paw-reaching-for-food task. GH treatment and rehabilitation at 35 dpi significantly improved the motor deficit caused by the injury and promoted an increase of cell proliferation in the PC ipsilateral to the injury, which could be involved in the improvement observed. Cortical ablation promoted a greater number of BrdU+ cells in the piriform cortex that was maintained long-term, which could be involved in the compensatory mechanisms of the brain after injury.
Conservative treatment of pelvic floor dysfunction (PFD) includes therapeutic exercise for pelvic floor muscle (PFM) training or other complementary exercise modalities, such as hypopressive ...exercises. However, the long-term effectiveness of the conservative treatment depends on a patient's adherence to the exercises and the integration of professional health advice into their daily life. The objective of this study was to establish the adherence experience of women with diagnosed PFD in home-based exercises after an intensive face-to-face physiotherapy treatment. A qualitative study from an interpretive paradigm was developed. Semi-structured individual and group interviews were performed 6 months after finishing individual physiotherapy treatment. The interviews were recorded, fully transcribed and analyzed thematically by creating categories. Thirty-one women were interviewed. The women reported that their adherence to home PFM exercises depended on the exercise program itself, its efficacy, their personal experiences with the exercises, intrinsic factors such as self-awareness or beliefs, and extrinsic factors, such as professional or instrumental feedback. Thus, therapeutic adherence could be more likely with effective physiotherapy programs that include mutually agreed home exercises and simple movements women can build into their daily lives. Improving awareness and knowledge of the pelvic region and the importance of PFM treatment as well as consideration for potential worsening of PFD will also encourage women to adhere to the exercises.
Microglial dysfunction plays a causative role in Alzheimer's disease (AD) pathogenesis. Here we focus on a germline insertion/deletion variant mapping SIRPβ1, a surface receptor that triggers ...amyloid-β(Aβ) phagocytosis via TYROBP.
To analyze the impact of this copy-number variant in SIRPβ1 expression and how it affects AD molecular etiology.
Copy-number variant proxy rs2209313 was evaluated in GERALD and GR@ACE longitudinal series. Hippocampal specimens of genotyped AD patients were also examined. SIRPβ1 isoform-specific phagocytosis assays were performed in HEK393T cells.
The insertion alters the SIRPβ1 protein isoform landscape compromising its ability to bind oligomeric Aβ and its affinity for TYROBP. SIRPβ1 Dup/Dup patients with mild cognitive impairment show an increased cerebrospinal fluid t-Tau/Aβ ratio (p = 0.018) and a higher risk to develop AD (OR = 1.678, p = 0.018). MRIs showed that Dup/Dup patients exhibited a worse initial response to AD. At the moment of diagnosis, all patients showed equivalent Mini-Mental State Examination scores. However, AD patients with the duplication had less hippocampal degeneration (p < 0.001) and fewer white matter hyperintensities. In contrast, longitudinal studies indicate that patients bearing the duplication allele show a slower cognitive decline (p = 0.013). Transcriptional analysis also shows that the SIRPβ1 duplication allele correlates with higher TREM2 expression and an increased microglial activation.
The SIRPβ1 internal duplication has opposite effects over MCI-to-Dementia conversion risk and AD progression, affecting microglial response to Aβ. Given the pharmacological approaches focused on the TREM2-TYROBP axis, we believe that SIRPβ1 structural variant might be considered as a potential modulator of this causative pathway.
The purpose of this study was to check the efficacy and safety of a novel tear substitute containing hyaluronic acid and low-dose hydrocortisone in the treatment of moderate dry eye disease.
In this ...prospective randomized study, 38 patients with moderate dry eye disease were divided into two treatment groups: Group 1 received one drop of 0.2% sodium hyaluronate and 0.001% hydrocortisone four times daily for 3 months, while Group 2 received 0.15% sodium hyaluronate and 3% trehalose at the same dosage. OSDI and SANDE questionnaires, Non-Invasive Break-Up time (NIBUT), Tear Meniscus Height (TMH), meibography, Lipid Layer Thickness (LLT), Tear Break-Up Time (TBUT), Corneal Staining Score (CFS), and Intraocular Pressure (IOP) were evaluated at baseline and after 1, 2, and 3 months of treatment.
During the treatment period, Group 1 showed statistically significant improvement in OSDI score (
= 0.002), SANDE score (
= 0.01), NIBUT (
< 0.0001), LLT (
< 0.0001), TBUT (
= 0.01), and CFS (
= 0.02). In Group 2, significant improvement was observed only in the TBUT score (
< 0.05). Comparison of the two groups showed that NIBUT and LLT were significantly different at the end of treatment (
= 0.001 for both comparisons), with more favorable results for sodium hyaluronate and hydrocortisone than for sodium hyaluronate and trehalose. No significant variations in intraocular pressure were observed in either group during the treatment period (
> 0.05).
: The study confirms that a 3-months treatment with hyaluronic acid 0.2% in combination with low-dose hydrocortisone 0.001% improves the signs and symptoms of moderate DED and that a low-dosage 0.001% hydrocortisone can be helpful in preventing the progression to chronic stages of DED.
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